1. Field of the Invention
The invention relates to cosmetic and pharmaceutical formulations such as (a) stick formulations and (b) formulations comprising a liquid dispersion medium.
In particular the invention relates to:
(a) essentially anhydrous cosmetic stick formulations such as lip balms, lipsticks, and underarm deodorant or antiperspirant sticks, and
(b) essentially anhydrous formulations comprising a liquid dispersion medium, e.g. anhydrous aerosol spray formulations such as deodorant, antiperspirant or perfume sprays.
Application of a topical biological active agent directly to skin results in an initial burst of activity. However, this activity phases out quickly. Accordingly, to prolong or delay activity, the active agent must be formulated into a product which gradually releases active agent. It is even more preferred to formulate the product in such a manner that the active agent is released precisely at the time of greatest need. Consumers expect a high level of sophistication in their products. There is thus a need for an intelligent skin care product which can provide not only prolonged release of active agent, but which also coordinates peak delivery of active agent to a particular biological demand. This responsive delivery is referred to herein as controlled delivery.
2. Description of the Related Art
In recent years increasing attention has been paid to the development of liposomes for use as microscopic xe2x80x9ccontainersxe2x80x9d. Liposomes have been used to deliver active agent to the skin. For example, U.S. Pat. No. 5,128,139 (Brown et al.) teaches a deodorant comprising liposomes containing grapefruit seed extract. The bioactive agents are entrapped within multilamellar liposomes complexes to provide release over time. Brown et al. acknowledge that liposomes are inherently unstable and tend to break apart, releasing the contents within. Brown et al. thus layers the liposomes or forms them into clusters such that the liposomes which are confined within or are sandwiched between outer layers of liposomes are protected and are more likely to remain stable, while the outer xe2x80x9csacrificialxe2x80x9d liposomes tend to break apart releasing their contents during product formulation. This premature release of liposome content is undesirable where the liposome content is a high-value or potent active agent. Further, this formulation does not provide controlled release, i.e., co-ordination of release in response to biologic demand. U.S. Pat. No. 4,937,078 to Mezie et. al. discloses the incorporation of topical anesthetic active agents into liposomes which essentially encapsulate the active ingredient within layers of lipid material. It is reported that these lipid vesicles provide a more pronounced cutaneous anesthetic or analgesic effect while employing less of the topical anesthetic agent. The lipid vesicles allegedly provide a means of prolonging the permeation rate without the risk for discomfort due to numbness or systemic reactions. However, prolonging release simply refers to constant rate of release over an extended period of time. There is no mention of suppressing active agent until triggered by a biologic need, then releasing an amount of active agent commensurate with the need.
U.S. Pat. No. 5,510,120 (Jones, et al.) teaches a cosmetic composition for topical application to the skin and/or hair. The composition comprises microcapsules or liposomes which enclose a cosmetically-effective benefit agent (e.g., an agent intended to modify or enhance body odor) active at a target location accessible by application to the skin and/or hair. The particles have means, namely lectin, for binding to targeted microorganisms present on the skin and/or hair, for example those bacteria responsible for skin disorders, scalp irritation, and underarm and foot odor. The encapsulated active agent may be used in combination with a vehicle or carrier such as water, various liquid substances, and various powders such as chalk, talc, fullers earth, kaolin, starch, gums, colloidal silica, etc. While Jones et al. teach targeting delivery of active agent in terms of location, they do little to target delivery in terms of time, i.e., controlling release to peak at the time of greatest need.
U.S. Pat. No. 5,783,211 (Manzo et al) describes the production of starch based particles which encapsulate active agents such as pharmaceutical or cosmetic active ingredients and provide controlled release of these active agents. The material produced according to this patent is a powdery cosmetic formulation, e.g., baby powder. As the starch absorbs moisture, the liposomes disintegrate resulting in the release of the active agent. The particles thus provide controlled release of the encapsulated active agent precisely at the time of need. Unfortunately, dry powder formulations are not suitable for use by most adults, since fine white powders do not remain on the skin and tend to migrate through clothes and show up particularly on the outside surface of dark clothes.
It would thus be of interest to be able to adapt the moisture triggered controlled release system of U.S. Pat. No. 5,783,211 to other cosmetic applications. However, liposomes are delicate, and it would be expected that active-agent containing liposomes would be destroyed during the process of formulating cosmetic stick products or aerosol spray products. Further, it would be expected that waxes and oleophilic organic ingredients of stick formulations and organic dispersion media (propellants) used in aerosol sprays would mask the liposomes, and interfere with the controlled release of active substance in response to biological demand.
Accordingly, there remains a need for a new type of delivery system which satisfies a number of requirements, namely, it must be capable of formulating even labile compounds, it must provide enhanced stability, it must be aesthetically pleasing, it must increase efficacy, and it must have reduced irritancy, it must remain in place, and most importantly, it must remain capable of releasing active ingredient in response to biological demand.
It is an object of the present invention to provide a pharmaceutical and/or cosmetic delivery system which provides controlled release of active agent, such as a bacteriostat, an anti-inflammatory agent, a fragrance, or a dye (e.g., a dye which changes color in reaction to change in pH, upon exposure to moisture, exposure to light, etc.).
Another objective of this invention is to provide a formulation which can be applied to skin and which remains on the skin.
Another objective of this invention is to provide a pharmaceutical and/or cosmetic delivery system in which diverse active ingredients such as Dragosantol and Farnesolm can be insulated from each other and other ingredients, and be protected from degradative processes such as oxidation.
It has now surprisingly been found that the dry powders formed in accordance with U.S. Pat. No. 5,783,211, though sensitive enough to decompose upon exposure to body moisture, are nevertheless sufficiently stable such that the particles stay enriched in active ingredient content during the process of manufacturing and storage of dry stick anhydrous cosmetic preparations and aerosol spray formulations.
Correspondingly, the invention provides a (preferably anhydrous) cosmetic or pharmaceutical product (formulation) comprising:
a solid or liquid dispersion medium, and
about 0.01-20 weight percent, based upon the total weight of said product, of particles dispersed in said dispersion medium, said particles comprising modified starch, liposomes containing biologically active agent, and, optionally, a hydrocolloid gum.
Typically, said particles have an average particle size in the range of 20-120 xcexcm.
Preferably said liposomes have a droplet size of from 100 to 1000 nm, more preferably from 200 to 300 nm.
Although anhydrous products (formulations) are always preferred, a water content of up to 5% by weight is acceptable in certain applications, in particular in solid cosmetic products.
A product according to the invention can be a cosmetic product wherein the dispersion medium is a solid lipophilic organic matrix comprising
10-55 wt. % volatile oil,
1-35 wt. % liquid emollient, and
12-30 wt. % low melting point wax.
Such a product is preferred, as far as solid cosmetic formulations are concerned.
Said volatile oil can advantageously be a cyclic or linear polydimethylsiloxane containing between 3-9 silicon atoms or a linear polydimethylsiloxane illustrated by the formula:
(CH3)3Sixe2x80x94O[Si(CH3)2xe2x80x94O]nxe2x80x94Si(CH3)3
where n is an integer with a value of about 1-7.
Additionally or alternatively, the volatile oil ingredient can comprise a C12-C20branched-chain hydrocarbon.
The liquid emollient ingredient is preferably a water-insoluble organic acid, ester or ether compound.
The wax ingredient is advantageously selected from C8-C30 alcohol, acid, ester and amide compounds.
The hydrocolloid gum optionally present in the product according to the present invention is preferably selected from the group consisting of xanthan, maltodextrin, galactomanan and tragacanth, maltodextrin being preferred.
The biologically active agent encapsulated in said liposomes can be selected from the group consisting of anti-inflammatory, antiphlogistic, antibacterial, anti-perspirant, astringent, and anti-fungal agents. In particular, the biologically active agent can be selected from the group consisting of bisabolol, tocopherol and farnesol.
Within the concept of the present invention cosmetic or pharmaceutical products are advantageously formed by a process comprising
(a) incorporating a biologically active agent into liposomes
(b) forming an aqueous mixture of active agent encapsulating liposomes, starch and, optionally, a hydrocolloid gum,
(c) spray drying said mixture to form a dry powder composition,
(d) dispersing said dry powder composition into a (preferably anhydrous) dispersion medium.
The dispersion obtained after step (d) can be further processed to give a cosmetic or pharmaceutical product. In step (d) the dispersion medium is chosen according to the desired properties of the product.
A solid cosmetic or pharmaceutical (preferably anhydrous) product is favourably formed by a process comprising steps
(a)-(c) as above,
(d) dispersing said dry powder composition into a solid (preferably anhydrous) lipophilic cosmetic matrix, and
(e) shaping the product of step (d).
A cosmetic or pharmaceutical anhydrous aerosole spray formulation is advantageously formed by a process comprising steps
(a)-(c) as above, and
(d) dispersing said dry powder composition into a (typically anhydrous) liquid dispersion medium.
If more than 50% of the small amount of water sometimes present in the cosmetic or pharmaceutical products according to the invention has already been present in the dry powder composition after spray drying (step (c)), the obtained product is considered to be xe2x80x9cessentially anhydrousxe2x80x9d. Within the concept of the present invention, essentially anhydrous cosmetic or pharmaceutical products are preferred as the dry powder composition (comprising the liposomes containing biologically active agent) within the product remains intact for a long time only in an essentially water-free environment.
The present invention utilizes the moisture triggered release technology of U.S. Pat. No. 5,783,211 (Manzo et al.), preferably for lipophilic active ingredients, and does this by incorporating these particles in an anhydrous (or nearly anhydrous) organic matrix.
More specifically, the objects of the invention are achieved by encapsulating active agents in liposomes, preferably nanosomes having an average diameter of approximately 200 nm, which are then mixed and spray dried with a carrier or matrix forming composition, preferably a water absorptive composition such as modified starch and preferably also maltodextrin, followed by incorporation of the resulting particles (dry powder) in an organic dispersion medium (solid or liquid) and (a) if the dispersion medium is solid (i.e. a matrix), forming the composition into a cosmetic stick such as a lip balm, an underarm deodorant stick or a lipstick, or (b) if the dispersion medium is liquid, dispersing the particles into the liquid dispersion medium. Liposomes act as the delivery agents for active agents such as Dragosantol(copyright), Farnesol(trademark), antiherpetically active substances, etc. As the water absorbent component of the particles according to the present invention absorbs water, it acts as a trigger on the intimately associated liposome component, triggering a loss of structural integrity in the liposome carrier followed by the release of the active agent. Thus, in response to a condition such as perspiration, the particles in the cosmetic stick according to the present invention release one or more of, e.g., an anti-perspirant, anti-microbial, cooling, tingling, anti-inflammatory agent, fragrance or dye (e.g., a dye which changes color in reaction to change in pH, upon exposure to moisture, exposure to light, etc.).
Within the concept of the present invention, cosmetic stick formulations could be solid (including semisolid) but anhydrous formulations as they are used to make, e.g., chap sticks, lipsticks or non-aqueous deodorant sticks.
Within the concept of the present invention, aerosol spray formulations can be anhydrous dispersions, suspensions or slurries, which have to be shaken before use. A liquid dispersion medium used within the concept of the invention, for example in an aerosol spray formulation, should be an (essentially) anhydrous liquid lipophilic medium (such as a propellant) and/or is preferably selected from the group consisting of (a) hydrocarbons, (b) fluorocarbons, (c) dimethylether, and (d) mixtures thereof.
By incorporating a moisture triggered release system as described in U.S. Pat. No. 5,783,211 into a cosmetic stick formulation or aerosol spray formulation a release of an active product could be achieved at a certain point during the application process. Not only is a prolongation of activity caused, but also a maximization, because the active agent will be held back for a longer period of time and released for peak activity in response to demand when it is ultimately needed. The active agent will not be wasted when not needed, and will be available to provide activity when needed and will last longer.
For example, a deodorizing agent could be released after application of a non-aqueous deodorant stick or aerosol spray when the person begins to sweat. This is the point when most activity is needed. Other possible activities might be: generation of a fragrance; release of a sensory stimulant such as releasing menthol to provide a cool sensation, releasing jambu (jambu oleoresin, an extract from Spilanthes acmella) to provide a tingling sensation, for example, on the lips in response to kissing, or otherwise generating a physiological skin activity; or providing a change or an enhancement in color intensity in, e.g., a lipstick, by timed release of dyes.
The foregoing has outlined rather broadly the more pertinent and important features of the present invention in order that the detailed description of the invention that follows may be better understood and so that the present contribution to the art can be more fully appreciated. Additional features of the invention will be described hereinafter. It should be appreciated by those skilled in the art that the conception and the specific embodiments disclosed may be readily utilized as a basis for modifying or designing other biologically active agent delivery systems for carrying out the same purposes of the present invention. It should also be realized by those skilled in the art that such equivalent structures and the processes for forming them do not depart from the spirit and scope of the invention as set forth in the appended claims.